Torção do ceco em touro nelore

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Attenuated T Cell Responses to a High-Potency Ligand In Vivo

According to this study, the strongest T cell receptor ligands in vitro do not necessarily induce the strongest T cell responses in vivo, suggesting that vaccine designers may need to reconsider their strategies

Degenerate T-cell Recognition of Peptides on MHC Molecules Creates Large Holes in the T-cell Repertoire

The cellular immune system screens peptides presented by host cells on MHC molecules to assess if the cells are infected. In this study we examined whether the presented peptides contain enough information for a proper self/nonself assessment by comparing the presented human (self) and bacterial or viral (nonself) peptides on a large number of MHC molecules. For all MHC molecules tested, only a small fraction of the presented nonself peptides from 174 species of bacteria and 1000 viral proteomes (0.2%) is shown to be identical to a presented self peptide. Next, we use available data on T-cell receptor-peptide-MHC interactions to estimate how well T-cells distinguish between similar peptides. The recognition of a peptide-MHC by the T-cell receptor is flexible, and as a result, about one-third of the presented nonself peptides is expected to be indistinguishable (by T-cells) from presented self peptides. This suggests that T-cells are expected to remain tolerant for a large fraction of the presented nonself peptides, which provides an explanation for the “holes in the T-cell repertoire” that are found for a large fraction of foreign epitopes. Additionally, this overlap with self increases the need for efficient self tolerance, as many self-similar nonself peptides could initiate an autoimmune response. Degenerate recognition of peptide-MHC-I complexes by T-cells thus creates large and potentially dangerous overlaps between self and nonself

Protective Effector Memory CD4 T Cells Depend on ICOS for Survival

Memory CD4 T cells play a vital role in protection against re-infection by pathogens as diverse as helminthes or influenza viruses. Inducible costimulator (ICOS) is highly expressed on memory CD4 T cells and has been shown to augment proliferation and survival of activated CD4 T cells. However, the role of ICOS costimulation on the development and maintenance of memory CD4 T cells remains controversial. Herein, we describe a significant defect in the number of effector memory (EM) phenotype cells in ICOS−/− and ICOSL−/− mice that becomes progressively more dramatic as the mice age. This decrease was not due to a defect in the homeostatic proliferation of EM phenotype CD4 T cells in ICOS−/− or ICOSL−/− mice. To determine whether ICOS regulated the development or survival of EM CD4 T cells, we utilized an adoptive transfer model. We found no defect in development of EM CD4 T cells, but long-term survival of ICOS−/− EM CD4 T cells was significantly compromised compared to wild-type cells. The defect in survival was specific to EM cells as the central memory (CM) ICOS−/− CD4 T cells persisted as well as wild type cells. To determine the physiological consequences of a specific defect in EM CD4 T cells, wild-type and ICOS−/− mice were infected with influenza virus. ICOS−/− mice developed significantly fewer influenza-specific EM CD4 T cells and were more susceptible to re-infection than wild-type mice. Collectively, our findings demonstrate a role for ICOS costimulation in the maintenance of EM but not CM CD4 T cells

Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies.

Cytolytic CD8 T cells play a crucial role in the control and elimination of virus-infected cells and are a major focus of HIV cure efforts. However, it has been shown that HIV-specific CD8 T cells are infrequently found within germinal centers (GCs), a predominant site of active and latent HIV infection. We demonstrate that HIV infection induces marked changes in the phenotype, frequency, and localization of CD8 T cells within the lymph node (LN). Significantly increased frequencies of CD8 T cells in the B cell follicles and GCs were found in LNs from treated and untreated HIV-infected individuals. This profile was associated with persistent local immune activation but did not appear to be directly related to local viral replication. Follicular CD8 (fCD8) T cells, despite compromised cytokine polyfunctionality, showed good cytolytic potential characterized by high ex vivo expression of granzyme B and perforin. We used an anti-HIV/anti-CD3 bispecific antibody in a redirected killing assay and found that fCD8 T cells had better killing activity than did non-fCD8 T cells. Our results indicate that CD8 T cells with potent cytolytic activity are recruited to GCs during HIV infection and, if appropriately redirected to kill HIV-infected cells, could be an effective component of an HIV cure strategy